IL-16 is a ligand and chemotactic factor for CD4+ T cells. IL-16 inhibits the CDS mediated lymphocyte activation and proliferation. The effects of IL-16 on the target cells are dependent on the cell type, the presence...IL-16 is a ligand and chemotactic factor for CD4+ T cells. IL-16 inhibits the CDS mediated lymphocyte activation and proliferation. The effects of IL-16 on the target cells are dependent on the cell type, the presence of co-activators etc. To understand the regulation function and mechanism of IL-16 on target cells, we used a 130 a.a. recombinant IL-16 to study its effects on the growth of Jurkat T leukemia cells in vitro. We found that the rIL-16 stimulated the proliferation of Jurkat cells at low dose (10-9M), but inhibited the growth of the cells at higher concentration (10-5M). Results showed that 10-5 M of rIL-16 treatment induced an enhanced apoptosis in Jurkat cells. The treatment blocked the expression of FasL, but up-regulated the c-myc and Bid expression in the cells. Pre-treatment of PKC inhibitor or MEK1 inhibitor markedly increased or decreased the rIL-16 induced growth-inhibiting effects on Jurkat cells, respectively. The results suggested that the rIL-16 might be a regulator for the growth or apoptosis of Jurkat cells at a dose-dependent manner. The growth-inhibiting effects of rIL-16 might be Fas/FasL independent, but, associated with the activation of PKC, up-regulated expression of c-Myc and Bid, and the participation of the ERK signal pathway in Jurkat cells.展开更多
The increased proliferation and migration of vascular smooth muscle cells （VSMCs） are key events in the development of atherosclerotic lesions. Baicalin, an herb-derived flavonoid compound, has been previously shown...The increased proliferation and migration of vascular smooth muscle cells （VSMCs） are key events in the development of atherosclerotic lesions. Baicalin, an herb-derived flavonoid compound, has been previously shown to induce apoptosis and growth inhibition in cancer cells through multiple pathways. However, the potential role of baicalin in regulation of VSMC proliferation and prevention of cardiovascular diseases remains unexplored. In this study, we show that pretreatment with baicalin has a dose-dependent inhibitory effect on PDGF-BB-stimulated VSMC pro- liferation, accompanied with the reduction of proliferating cell nuclear antigen （PCNA） expression. We also show that baicalin-induced growth inhibition is associated with a decrease in cyclin E-CDK2 activation and increase in p27 level in PDGF-stimulated VSMCs, which appears to be at least partly mediated by blockade of PDGF recep- tor [~ （PDGFR~）-extracellular signal-regulated kinase 1/2 （ERK1/2） signaling. In addition, baicalin was also found to inhibit adhesion molecule expression and cell migration induced by PDGF-BB in VSMCs. Furthermore, using an animal carotid arterial balloon-injury model, we found that baicalin significantly inhibited neointimal hyperplasia. Taken together, our results reveal a novel function of baicalin in inducing growth arrest of PDGF-stimulated VSMCs and suppressing neointimal hyperplasia after balloon injury, and suggest that the underlying mechanism involves the inhibition of cyclin E-CDK2 activation and the increase in p27 accumulation via blockade of the PDGFR^-ERK1/2 signaling cascade.展开更多
OBJECTIVE This study aimed to explore the expression and significance of transforming growth factor β1（TGF-β1）,extracellular signal-regulated kinases 1/2 （ERK1/2）, and K-ras in colorectal cancer （CRC） using ti...OBJECTIVE This study aimed to explore the expression and significance of transforming growth factor β1（TGF-β1）,extracellular signal-regulated kinases 1/2 （ERK1/2）, and K-ras in colorectal cancer （CRC） using tissue microarray technology.METHODS The expressions of TGF-β1, ERK1/2, and K-ras in colon cancer cells taken from the specimens of 92 CRC patients （stage Ⅰ： 16 cases, stage Ⅱ： 28 cases, stage Ⅲ： 24 cases, and stage Ⅳ：24 cases） were analyzed using tissue microarray technology and immunohistochemistry, and compared with those of 20 normal colon tissue samples.RESULTS High immunoreactive scores （IRS） of TGF-β1,p-ERK1/2, and K-ras protein in CRC were obtained, which were 66.3% （61/92）, 59.8% （55/92）, and 48.9% （45/92）, respectively, and those in normal epithelial cells of colon were 10% （2/20）, 20% （4/20）, and 30% （6/20）, respectively （P 〈 0.05）. The expressions of TGF-β1 and ERK1/2 in CRC at stage Ⅰwere 37.5% and 31.3%,respectively, and those in CRC at stage Ⅳ were 83.3% and79.3%, respectively, with statistically significant differences. No significant relationship was found between K-ras expression and tumor stages （P〉0.05）.CONCLUSION High level expressions of TGF-β1 and ERK1/2 are closely related to the clinical stages of colon cancer and crosstalk may exist between the 2 signal pathways.展开更多
Objective： To observe the effects of moxibustion pretreatment on the protein expressions of epidermal growth factor receptor （EGFR）, phosphorylation extracellular signal-regulated kinase I/2 （p-ERKI/2） and activa...Objective： To observe the effects of moxibustion pretreatment on the protein expressions of epidermal growth factor receptor （EGFR）, phosphorylation extracellular signal-regulated kinase I/2 （p-ERKI/2） and activated protein-1 （AP-2）, the key factors of extracellular signal-regulated kinase signaling transduction pathway in gastric tissue of rats with stress-induced gastric mucosal damage, and to discuss the mechanisms of moxibustion therapy in promoting the restoration of damaged gastric mucosa. Methods： Thirty Sprague-Dawley （SD） rats were randomly divided into a normal group, a model group, and a moxibustion group using the random digits table, 10 in each group. Except the rats in the normal group, rats in the other two groups were used to make stress-induced gastric mucosal damage model using restraint and cold stress. Before modeling, rats in the moxibustion group were alternately treated with moxibustion a/t Zusanli （ST 36） and Zhongwan （CV 12）, or Pishu （BL 20） and Weishu （BL 22）, once a day, for a total of 8 d. Histolo^cal changes of gastric mucosa were observed under the light microscopy, the expression of gastric tissue p-ERKI/2 was detected by immunohistochemistry assay, and the protein levels of EGFR and AP-I were measured by Western blots. Results： Compared with rats in the normal group, gastric mucosal damage was more serious, and protein expressions of gastric tissue EGFR, p-ERK1/2 and AP-1 increased in the model group （P〈0.01, P〈O.05, P〈0.05）. Compared with rats in the model group, gastric mucosal damage was milder, and protein expressions of gastric tissue EGFR, p-ERK1/2 and AP-1 increased in the moxibustion group （all P〈0.01）. Conclusion： Moxibustion at Zusanli （ST 36）, Zhongwan （CV 12）, Pishu （BL 20） and Weishu （BL 21） could increase EGFR, p-ERK1/2 and AP-1 expression levels in gastric tissue of stress-induced gastric mucosal damage rats, maintain the information transfer function of ERK signaling transduction pathway, and promote restoration of gastric mucosal damage.展开更多
文摘IL-16 is a ligand and chemotactic factor for CD4+ T cells. IL-16 inhibits the CDS mediated lymphocyte activation and proliferation. The effects of IL-16 on the target cells are dependent on the cell type, the presence of co-activators etc. To understand the regulation function and mechanism of IL-16 on target cells, we used a 130 a.a. recombinant IL-16 to study its effects on the growth of Jurkat T leukemia cells in vitro. We found that the rIL-16 stimulated the proliferation of Jurkat cells at low dose (10-9M), but inhibited the growth of the cells at higher concentration (10-5M). Results showed that 10-5 M of rIL-16 treatment induced an enhanced apoptosis in Jurkat cells. The treatment blocked the expression of FasL, but up-regulated the c-myc and Bid expression in the cells. Pre-treatment of PKC inhibitor or MEK1 inhibitor markedly increased or decreased the rIL-16 induced growth-inhibiting effects on Jurkat cells, respectively. The results suggested that the rIL-16 might be a regulator for the growth or apoptosis of Jurkat cells at a dose-dependent manner. The growth-inhibiting effects of rIL-16 might be Fas/FasL independent, but, associated with the activation of PKC, up-regulated expression of c-Myc and Bid, and the participation of the ERK signal pathway in Jurkat cells.
基金We are grateful to Dr Guan KL （Moore＇s Cancer Center, La Jolla, CA, USA） for the gift of pCMV-MEKca. This study was supported by the National Natural Science Foundation of China （30770787 and 90919035）, the National Basic Research Program of China （2005CB523301）, and the International Cooperation in Science and Technology Projects （2006DFB32460） and the Hebei Province Natural Science Foundation （C2007000831）.
文摘The increased proliferation and migration of vascular smooth muscle cells （VSMCs） are key events in the development of atherosclerotic lesions. Baicalin, an herb-derived flavonoid compound, has been previously shown to induce apoptosis and growth inhibition in cancer cells through multiple pathways. However, the potential role of baicalin in regulation of VSMC proliferation and prevention of cardiovascular diseases remains unexplored. In this study, we show that pretreatment with baicalin has a dose-dependent inhibitory effect on PDGF-BB-stimulated VSMC pro- liferation, accompanied with the reduction of proliferating cell nuclear antigen （PCNA） expression. We also show that baicalin-induced growth inhibition is associated with a decrease in cyclin E-CDK2 activation and increase in p27 level in PDGF-stimulated VSMCs, which appears to be at least partly mediated by blockade of PDGF recep- tor [~ （PDGFR~）-extracellular signal-regulated kinase 1/2 （ERK1/2） signaling. In addition, baicalin was also found to inhibit adhesion molecule expression and cell migration induced by PDGF-BB in VSMCs. Furthermore, using an animal carotid arterial balloon-injury model, we found that baicalin significantly inhibited neointimal hyperplasia. Taken together, our results reveal a novel function of baicalin in inducing growth arrest of PDGF-stimulated VSMCs and suppressing neointimal hyperplasia after balloon injury, and suggest that the underlying mechanism involves the inhibition of cyclin E-CDK2 activation and the increase in p27 accumulation via blockade of the PDGFR^-ERK1/2 signaling cascade.
基金This work was supported by grants from Soochow University Students Innovation Foundation （No. 5731512810）, Chinese National Natural Science Foundation （No.81072186）, and Jiangsu Provincial Higher Institution Natural Science Foundation （No.10KJB320018）.
文摘OBJECTIVE This study aimed to explore the expression and significance of transforming growth factor β1（TGF-β1）,extracellular signal-regulated kinases 1/2 （ERK1/2）, and K-ras in colorectal cancer （CRC） using tissue microarray technology.METHODS The expressions of TGF-β1, ERK1/2, and K-ras in colon cancer cells taken from the specimens of 92 CRC patients （stage Ⅰ： 16 cases, stage Ⅱ： 28 cases, stage Ⅲ： 24 cases, and stage Ⅳ：24 cases） were analyzed using tissue microarray technology and immunohistochemistry, and compared with those of 20 normal colon tissue samples.RESULTS High immunoreactive scores （IRS） of TGF-β1,p-ERK1/2, and K-ras protein in CRC were obtained, which were 66.3% （61/92）, 59.8% （55/92）, and 48.9% （45/92）, respectively, and those in normal epithelial cells of colon were 10% （2/20）, 20% （4/20）, and 30% （6/20）, respectively （P 〈 0.05）. The expressions of TGF-β1 and ERK1/2 in CRC at stage Ⅰwere 37.5% and 31.3%,respectively, and those in CRC at stage Ⅳ were 83.3% and79.3%, respectively, with statistically significant differences. No significant relationship was found between K-ras expression and tumor stages （P〉0.05）.CONCLUSION High level expressions of TGF-β1 and ERK1/2 are closely related to the clinical stages of colon cancer and crosstalk may exist between the 2 signal pathways.
基金supported by National Basic Research Program of China(973 Program,No.2015CB554502)National Natural Science Foundation of China(No.81202770,No.81574082)+5 种基金Special Research Fund for the Doctoral Program of Higher Education of China for New Teachers(No.20124323120002)Hunan Provincial Natural Science Foundation of China(No.13JJ6060)Foundation for the Author of Excellent Doctoral Dissertation of Hunan Province(No.YB2013B037)Fund Project of Hunan Province Education Office(No.14B129)2013 Project of Scientific and Technological Innovation and Entrepreneurship Platform for Huxiang Youth2013 Training Project of 225 for High-level Medical Personnel of Hunan Province~~
文摘Objective： To observe the effects of moxibustion pretreatment on the protein expressions of epidermal growth factor receptor （EGFR）, phosphorylation extracellular signal-regulated kinase I/2 （p-ERKI/2） and activated protein-1 （AP-2）, the key factors of extracellular signal-regulated kinase signaling transduction pathway in gastric tissue of rats with stress-induced gastric mucosal damage, and to discuss the mechanisms of moxibustion therapy in promoting the restoration of damaged gastric mucosa. Methods： Thirty Sprague-Dawley （SD） rats were randomly divided into a normal group, a model group, and a moxibustion group using the random digits table, 10 in each group. Except the rats in the normal group, rats in the other two groups were used to make stress-induced gastric mucosal damage model using restraint and cold stress. Before modeling, rats in the moxibustion group were alternately treated with moxibustion a/t Zusanli （ST 36） and Zhongwan （CV 12）, or Pishu （BL 20） and Weishu （BL 22）, once a day, for a total of 8 d. Histolo^cal changes of gastric mucosa were observed under the light microscopy, the expression of gastric tissue p-ERKI/2 was detected by immunohistochemistry assay, and the protein levels of EGFR and AP-I were measured by Western blots. Results： Compared with rats in the normal group, gastric mucosal damage was more serious, and protein expressions of gastric tissue EGFR, p-ERK1/2 and AP-1 increased in the model group （P〈0.01, P〈O.05, P〈0.05）. Compared with rats in the model group, gastric mucosal damage was milder, and protein expressions of gastric tissue EGFR, p-ERK1/2 and AP-1 increased in the moxibustion group （all P〈0.01）. Conclusion： Moxibustion at Zusanli （ST 36）, Zhongwan （CV 12）, Pishu （BL 20） and Weishu （BL 21） could increase EGFR, p-ERK1/2 and AP-1 expression levels in gastric tissue of stress-induced gastric mucosal damage rats, maintain the information transfer function of ERK signaling transduction pathway, and promote restoration of gastric mucosal damage.
